Facial palsy after administration of immune checkpoint inhibitors: case report, literature review and clinical care management.

Neurological immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI) are rare complications of immunotherapy, particularly dreadful for patients and clinical teams. Indeed, neurological irAEs are potentially severe and their diagnosis require prompt recognition and treatment. Additionally, the spectrum of neurological irAEs is broad, affecting either neuromuscular junction, peripheral or central nervous system. Here, we described the case of a 55-year man with metastatic melanoma, facing a brutal right peripheral cerebral palsy after his third ipilimumab/nivolumab infusion. After the case presentation, we reviewed the literature about this rare complication of immunotherapy, and described its diagnosis work-up and clinical management.

Ultrasound-Guided Injections for Treatment of Facial Paralysis Sequelae: A Randomized Study on Body Donors.

BACKGROUND: Botulinum toxin injection is the accepted standard treatment for synkinesis and gustatory hyperlacrimation in patients with facial paralysis. However, poor injection accuracy can result in inconsistent treatment outcomes, variable treatment durations, and complications. Ultrasound guidance should increase injection accuracy in the facial region; however, this has not been proven. METHODS: Twenty-six hemifaces of nonembalmed cadavers were studied in a randomized split-face manner. Ink was injected with ultrasound or landmark guidance into the lacrimal gland and three common synkinetic muscles: the orbicularis oculi, depressor anguli oris, and mentalis. Injection accuracy was evaluated using several measures. RESULTS: Using ultrasound guidance, most ink (>50%) was found inside the correct target in 88% of cases, compared with 50% using landmark guidance ( P < 0.001). This was most pronounced in the lacrimal gland (62% versus 8%), depressor anguli oris (100% versus 46%), and mentalis (100% versus 54%) ( P < 0.05). All ink was found inside the correct target (no ink outside) in 65% using ultrasound guidance versus 29% without ( P < 0.001). Injection accuracy (any ink in target) was 100% when using ultrasound guidance versus 83% without ( P < 0.01). Twenty-three percent of the landmark-guided depressor anguli oris injections stained the facial artery ( P = 0.22). CONCLUSIONS: Ultrasound guidance significantly increased injection accuracy and reduced the amount of ink lost in the surrounding tissue compared with landmark guidance. Clinical trials are needed to explore the effects of ultrasound guidance on treatment outcome, duration, and complications in patients with facial paralysis.

Comparison of treatment modalities for non-tuberculous mycobacterial cervicofacial lymphadenitis in children.

PURPOSE: We aim to compare the different treatment modalities of non-tuberculous cervicofacial lymphadenitis in children, by means of a retrospective study conducted in the University Hospitals of Leuven of patients treated between 2012 and 2022. METHODS: For this retrospective cohort study, data were collected and pseudonimised from 52 patients with non-tuberculous cervicofacial lymphadenitis, who were treated in our hospital between January 2012 and December 2022, either conservatively, antibiotically, surgically, or with a combination of these options. We only included patients who were considered immunocompetent. All of the included patients were below 10 years at time of treatment. We collected data regarding time to resolution and adverse effects, i.e., skin discoloration, excessive scar formation, fistula formation, persistence of adenopathies after treatment, need for additional treatment, facial nerve paresis/paralysis, or systemic side-effects due to antibiotic treatment. RESULTS: The mean time to resolution (in days) when looking at primary treatments, was shortest in partial excisions (16), followed by complete excisions (19), antibiotic therapy (129), incision and drainage (153), curettage (240), and finally conservative management (280). Taking into account isolated treatments (i.e., both primary and adjuvant), we also observed consistently faster time to resolution in surgical and antibiotic treatments when compared to conservative treatment. Antibiotic therapy (p = 0.003), incision and drainage (p = 0,004) were associated with a significantly higher need for adjuvant treatment. Curettage was associated with a higher incidence of fistula formation (p = 0,006) and higher number of adjuvant treatments (p = 0,002). CONCLUSIONS: This study shows a faster resolution of nontuberculous mycobacterial cervicofacial lymphadenitis in children when treated surgically, more specifically when treated with partial or complete lymph node excision. Antibiotic treatment also leads to faster resolution than conservative management. There was a low rate of complications, and no permanent facial nerve damage was reported.

Predictive role of facial nerve palsy improvement in malignant external otitis.

PURPOSE: To evaluate the effects of different factors on facial nerve palsy improvement in patients with malignant external otitis (MEO) and the predictive role of improvement on MEO. METHODS: Data were collected from all MEO patients with facial paralysis who were hospitalized between 2012 and 2017 at a tertiary referral center. We contacted patients at least 6 months after their admission to evaluate their facial nerve function and survival rate. RESULTS: In a study of 19 samples with a mean age of 69.1 years, 9 patients (47.7%) had some or complete improvement, while 10 (52.6%) had no or very minimal improvement. In this study, there was no statistically significant difference between patients with and without facial nerve palsy improvement in terms of age, sex, usage of antifungal treatment alongside antibiotics, duration of hospital stays, HbA1c level, presentation of hearing loss and vertigo, the severity of facial palsy, comorbidity score, mean of fasting blood sugar, leukocytosis, first ESR and ESR drop, CRP and physiotherapy. We found a positive correlation between improving facial palsy and patients' survival rates. CONCLUSION: Considering the possible influence of facial paralysis improvement prognosis on MEO patients' survival, it could affect our approach to the disease.

Comparison of oral versus intravenous steroid in the management of Bell's palsy: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Bell's palsy is a condition affecting cranial nerve VII that results in acute peripheral unilateral facial weakness or paralysis of unclear etiology. Corticosteroids are the primary therapy choice, because they improve outcomes. According to a recent study, prednisolone effectively treats Bell's palsy in the short and long term. This study aimed to assess the effectiveness and safety of Single-Dose Intravenous Methylprednisolone to Oral Prednisolone in treating Bell's palsy patients. METHODS: PRISMA statement guidelines were used to design and conduct this systemic review. MEDLINE, Cochrane Library, and EMBASE databases were used in our search. We conducted the database search in November 2022. RESULTS: Thirty-three publications were reviewed as a result of the literature review. Three studies were included in the meta-analysis after applying our criteria. 317 Bell's palsy patients were included in our study. Regarding complete recovery to grade 1 in 1 month, IV methylprednisolone was higher than oral prednisolone; (log OR = 0.52, 95% CI [0.08, 0.97], P = 0.022). However, at 3 months, the two groups had no significant difference. Patients with grade 4 Bell's palsy were more likely to fully recover to grade 1 in 1 month with IV methylprednisolone than with oral prednisolone (log OR = 0.73, 95% CI [0.19, 1.26], P = 0.008), but not for patients with grade 3 or grade 2 Bell's palsy. CONCLUSION: This study shows evidence that patients with Bell's palsy can fully recover to grade 1 in 1 month when IV methylprednisolone is used instead of oral prednisolone. At 3 months, however, there was no discernible difference between the two treatments. Within 3 days of the onset of symptoms, IV methylprednisolone treatment can be started, which may help patients recover fully to grade 1 in 1 month. However, administering IV methylprednisolone may not always have long-term advantages compared to oral prednisolone.

Improvement in Epiphora Using TEARS Grading Following Surgical Treatment of Meibomian Gland Inversion in Patients With Facial Nerve Palsy.

PURPOSE: To assess epiphora outcomes using the TEARS grading score in patients with concomitant meibomian gland inversion (MGI) and facial nerve palsy (FNP) undergoing correction of MGI. METHODS: Retrospective, 5-year, noncomparative, single-center study of patients with MGI and FNP, treated with MGI correction, under the supervision of a single surgeon. A validated "TEAR" score was used to assess changes in epiphora. RESULTS: Ten patients with FNP, MGI, and epiphora were analyzed from a group of 160 patients with FNP who underwent MGI surgery between 2017 and 2022. The mean age at surgery was 50 years (range, 13-76 years). T, E, and A scores significantly improved (p < 0.05). Eighty percent of patients saw a reduction in tearing frequency (T), with 60% gaining ≥ 2-grade improvement. Improvements in clinical effects (E) and activity limitation (A) were seen in 80% of patients, with 40% and 50% gaining ≥ 2-grade improvement, respectively. R scores (related to reflex tearing) improved by 60%, with 40% seeing ≥ 2-grade improvement. Nine patients (90%) improved symptomatically with an average improvement "S" score of 65% over a mean follow-up period of 30 months. All patients demonstrated restoration of the normal anatomical position of the meibomian glands. CONCLUSIONS: MGI can cause epiphora in patients with FNP and may explain cases where symptoms persist despite standard surgical intervention. This study provides proof of concept that MGI correction can improve epiphora and that identifying MGI may be considered a critical step in the treatment algorithm for epiphora in patients with FNP.

Botulinum toxin treatment of the buccinator muscle facial synkinesis: A systematic review.

BACKGROUND: The purpose of this review is to provide an overview of the available literature assessing the treatment of botulinum toxin injections for the treatment of synkinesis of the buccinator muscle in patients with peripheral facial palsy (PFP). MATERIALS AND METHODS: A multi database search was performed, including the following databases: Pubmed, Medline, Embase, and the Cochrane Library. Each database was searched from its earliest date until 8 June 2023. The following outcome measures were extracted from the articles when available: subjective, somatic, and psychological effects on the patients and objective outcomes such as the House-Brackmann, Sunnybrook and Sydney scores. The methodological quality of the included studies was rated using the Newcastle-Ottawa scale for nonrandomised trials. RESULTS: The primary literature search generated 37 articles. After removing duplicates, 25 articles remained for abstract appraisal, of which 20 underwent full-text appraisal, resulting in 3 studies for analysis. All of these studies showed (significant) improvement in synkinesis either measured using the Synkinesis Assessment Questionnaire or subjectively measured by asking treated patients. CONCLUSION: The available literature supports the finding that botulinum toxin treatment of the buccinator muscle could be a welcome addition to facial synkinesis treatment and could significantly improve patient outcomes. In future studies, the efficacy of EMG-guided buccinator injections, optimal dose, and a validated measuring method could be beneficial in optimising treatment for patients with a PFP and synkinesis.

Botulinum Toxin in Facial Reanimation: Map of the Facial Musculature and Dosage.

Recovery from flaccid facial paralysis can lead to the development of postfacial paralysis synkinesis. Chemodenervation, or treatment with botulinum toxin (BT), is a common treatment for individuals with synkinesis. Patients should be assessed in a multidisciplinary setting to create a specific, individualized, and targeted chemodenervation regimen. This article highlights relevant facial musculature, anatomy, suggested injection patterns, and BT dosages for treating synkinesis patients. These patients require postinjection follow-up, and they should be evaluated by a specially trained facial physical therapist for facial retraining.

Botulinum toxin A treatment in facial palsy synkinesis: a systematic review and meta-analysis.

BACKGROUND: Synkinesis is defined as involuntary movements accompanying by voluntary movements and can occur during the aftermath of peripheral facial palsy, causing functional, aesthetic and psychological problems in the patient. Botulinum toxin A (BTX-A) is frequently used as a safe and effective treatment; however, there is no standardized guideline for the use of BTX-A in synkinesis. The purpose of this article is to review and summarize studies about the BTX-A treatment of synkinesis in patients with a history of peripheral facial palsy; including given dosages, injection sites and time intervals between injections. MATERIALS AND METHODS: A multi-database systematic literature search was performed in October 2020 using the following databases: Pubmed, Embase, Medline, and The Cochrane Library. Two authors rated the methodological quality of the included studies independently using the 'Newcastle-Ottawa Quality Assessment Scale' for non-randomised studies' (NOS). RESULTS: Four-thousand-five-hundred-and-nineteen articles were found of which 34 studies met the inclusion criteria, in total comprising 1314 patients. Most studies were assessed to be of 'fair' to 'good' methodological quality. The Cohen's kappa (between author FJ and AS) was 0.78. Thirty-one studies investigated the reported dosage injected, 17 studies reported injection location and 17 studies investigated time intervals. A meta-analysis was performed for three studies comprising 106 patients, on the effects of BTX-A treatment on the Synkinesis Assessment Questionnaire (SAQ) scores. The mean difference was 11.599 (range 9.422-13.766), p < 0.01. However, due to inconsistent reporting of data of the included studies, no relationship with the dosage and location could be assessed. CONCLUSIONS: Many treatment strategies for synkinesis exist, consisting of varying BTX-A brands, dosages, time intervals and different injection locations. Moreover, the individual complaints are very specific, which complicates creating a standardized chemodenervation treatment protocol. The BTX-A treatment of long-term synkinesis is very individual and further studies should focus on a patient-tailored treatment instead of trying to standardize treatment.

Immunoglobulin G4-Related Disease Presenting as Temporal Bone Lesion with Facial Nerve Palsy.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic condition which could present as local infiltration of skull base structures. We report a case of IgG4-RD with infiltration of the temporal bone and surrounding structures in a patient with systemic vasculitis on systemic steroids. A 31-year-old woman presented with right-sided facial weakness, headache, and right ear hearing loss. On examination, redness and retraction of the right tympanic membrane and facial paresis (House-Brackman IV) were noted. Computed tomography imaging showed mastoiditis, temporal lobe stroke, and brain abscess. Magnetic resonance imaging (MRI) showed infiltration in the infratemporal fossa, nasopharynx, spreading along the Eustachian tube and perineurally along the branches of CN V and CN VII intracranially, forming a dural based mass in the middle cranial fossa. Intracranial mass compressed the temporal lobe of the brain, causing perifocal brain edema. Endoscopic biopsy of the nasopharynx was chosen as the least invasive method. It showed marked fibrosis of the tissue, dense lymphoplasmacytic infiltrates, and an increased number of IGG4-positive plasma cells. Serum IgG4 levels were below the diagnostic criteria of IgG4-RD, but histological characteristics of IgG4-RD were met. The patient was treated with high-dose oral prednisolone. Resolution of symptoms, including facial nerve paresis, was observed and infiltration in the nasopharynx, infratemporal fossa decreased on subsequent MRI tests. No recurrence was noted on the follow-up of 16 months. The case presented itself as a diagnostic challenge for a multidisciplinary team to differentiate pathology caused by either IgG4-RD, systemic vasculitis, or atypic mastoiditis. MRI and histological reports were essential to establish a correct diagnosis.

Management of Post-Facelift Facial Paralysis With Botulinum Toxin Type A.

BACKGROUND: Facial nerve injury after facelift is rare; hence, its treatment is poorly established. Botulinum toxin type A (BTXA) can be employed to resolve the asymmetry. To our knowledge, there is no protocol in the literature about the best timing for this treatment, injection sites, or recommended dose. OBJECTIVES: The authors sought to propose a protocol to guide the management of asymmetries post-facelift. METHODS: Fifteen patients with post-rhytidectomy facial palsies were treated in the non-paralyzed side with BTXA. After analysis of the smile deviation vectors, it is possible to identify the muscles that should be treated. The dose varied from 1 to 2 volume-unit per point. Patients were examined after 15 days for outcomes evaluation and touch-up if needed. Patients were re-treated after 5 to 6 months in case of asymmetry recurrence. RESULTS: Symmetry was achieved in all cases. Six patients had definitive nerve lesions and required treatment every 6 months after the first session. Five patients had lesions affecting the upper third of the face; 4 of them were definitive nerve lesions. Two of the 4 patients who were treated less than 2 weeks after surgery recovered early from the post-facelift paralysis and developed reversed asymmetry due to the BTXA. In 7 patients, the post-facelift asymmetry was due to neuropraxis: the recovery from the nerve injury and BTXA treatment occurred symmetrically on both sides of the face in the following months after 1 single session. CONCLUSIONS: Asymmetries post-facelift were successfully managed with the proposed protocol. The best time for injection was 2 to 4 weeks after surgery.

Cost of peripheral facial palsy treatment with Botulinum Toxin type A.

INTRODUCTION: Facial palsy (FP) is one of the most common neuropathies. Overall, 15%-30% of patients develop chronic sequelae. Several studies support the use of botulinum toxin A (BoNT-A) in the treatment of FP sequelae. No studies have analyzed the cost of treating FP with BoNT-A. METHODS: A retrospective review of data from all clinical records of consultations and procedures that took place at the FP Treatment Unit clinic throughout 2017. Type of BoNT-A used, total dose used, unilateral or bilateral injection, date of consultation, and gender were collected. The price of expendable materials, BoNT-A, and the 2017 salary scale was obtained to establish costs. RESULTS: During 2017, 605 clinical procedures were conducted in 240 patients. The mean number of procedures was 2.5 (0.80). The average time between procedures was 124(28.72) days. The total annual cost was 34.155,10€. The average annual cost of BoNT-A for each procedure was 39,93€, and the total annual cost of BoNT-A was 24.160,58€. On average, more units of IncotoxA were injected. This difference is not reflected in the final cost of each BoNT-A. For patients who achieved treatment stability, the average annual cost per patient was 106,6€ (OnatoxA) and 100,6€ (IncotoxA). CONCLUSION: In our unit, treatment with BoNT-A in FP sequelae had an average annual cost of 124,31€ per patient, requiring a visit to the hospital to receive treatment every 124 days. Given the functional and quality of life improvements, we should consider that it is a beneficial treatment at an acceptable cost.

Sjogren's syndrome associated with bilateral peripheral facial paralysis.

Sjogren's Syndrome (SS) is a chronic autoimmune disorder that may be complicated by neurological dysfunctions. The involvement of cranial nerves in SS was described as a very rare complication. Moreover, bilateral peripheral facial paralysis associated with SS has been described only in 3 patients in the literature and the first case was described by Henrik Sjogren himself in 1935. We report a 59-year-old female with bilateral peripheral facial paralysis associated with Sjogren's syndrome. She was treated with 5-day IVIG consecutively and continued oral methylprednisolone 16mg/day and almost fully recovered at 2 months of follow-up examination. Acute bilateral peripheral facial palsy in SS is a very rare condition and Lyme disease, Guillain-Barré syndrome, HIV infection, and central nervous system lymphoma should be considered in the differential diagnosis. As a result, SS should be considered as an underlying cause of bilateral facial paralysis.

Leptomeningeal relapse in primary cutaneous DLBCL: Implications for a prophylactic CNS therapy.

BACKGROUND: Isolated leptomeningeal relapse in a case of cutaneous lymphoma is an uncommon event more so in a case of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL). This phenomenon is of great significance as the subsequent prognosis becomes poor and the prophylactic central nervous system (CNS) therapy if administered, can reduce the chances of relapse, however, the survival benefit remains uncertain. The role of prophylactic CNS therapy is not well defined in the case of PCDLBCL. CASE: We report a case of PCDLBCL leg type with a low CNS International Prognostic Index (CNS-IPI) risk, who developed isolated leptomeningeal relapse in the form of bilateral facial nerve palsy. He was managed by 2nd line chemotherapy and CNS directed therapy and achieved complete remission. CONCLUSION: PCDLBCL leg type is an aggressive malignancy. Molecular/genomic mechanism likely responsible for CNS dissemination should be identified by prospective multi-centric studies that can better define the subsets of patients eligible for prophylactic therapy in the absence of a high CNS-IPI risk.

Effect of Bumetanide on Facial Nerve Regeneration in Rat Model.

OBJECTIVE: We investigated the effects of bumetanide alone and in combination with dexamethasone on facial nerve regeneration in rats with facial paralysis. STUDY DESIGN: A prospective controlled animal study. SETTING: An animal laboratory. SUBJECTS AND METHODS: Facial paralysis was induced in 32 Wistar rats that we then divided into 4 groups: group 1, control; group 2, bumetanide; group 3, dexamethasone; group 4, bumetanide and dexamethasone. Electroneurography was performed 1, 2, and 4 weeks later, and nerve regeneration was evaluated by electron and light microscopy and Western blotting in week 4. RESULTS: Regarding the comparison between preoperative values and week 4, the latency difference in group 1 (1.25 milliseconds) was significantly higher than those of groups 2 to 4 (0.56, 0.34, and 0.10 milliseconds, respectively; P = .001). The latency increment in groups 2 and 3 was higher than that of group 4 (P = .002 and P = .046) in week 4, whereas groups 2 and 3 did not differ significantly (P = .291). Amplitude difference was not statistically significant from week 4 among all groups (all P > .05). The number of myelinated axons was significantly higher in all treatment groups than in the control group (P = .001). Axon number and intensity were significantly higher in group 4 as compared with groups 2 and 3 (P = .009, P = .005). CONCLUSION: After primary neurorrhaphy, dexamethasone and bumetanide alone promoted nerve recovery based on electrophysiologic and histologic measures. Combination therapy was, however, superior.

Does Botulinum Toxin Therapy Improve Quality of Life in Patients with Facial Palsy?

OBJECTIVES: To review the current literature for the efficacy of botulinum toxin therapy to improve quality of life in patients with facial palsy. METHODS: A comprehensive systematic literature search was performed of the Medline, EMBase, PubMed and Cochrane Library databases. The population of interest was patients with facial palsy and the intervention of interest was botulinum toxin injection. The primary outcome of this review was quality of life outcomes before and after treatment. RESULTS: Six studies were included for review. Outcome data were not amenable to meta-analysis due to the heterogeneity of outcome measures. There was an overall trend towards improvement in quality of life after botulinum toxin therapy with the majority of studies demonstrating a statistically significant benefit. The aspects of life in which patients saw benefit varied amongst studies. No patient factors were identified to predict which sub-cohort would likely have the greatest benefit from therapy. Two studies reported adverse effects to be common however minor in nature. CONCLUSION: This review presents contemporary evidence that botulinum toxin is of benefit to the quality of life of patients with facial palsy. Additional larger randomised control trials would aid clinicians in quantifying the benefit of such therapies for patients with facial palsy. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Bilateral facial nerve involvement in a patient with Tolosa-Hunt syndrome.

Tolosa-Hunt syndrome is characterized by unilateral retro-orbital headaches and cranial nerve palsies, usually involving cranial nerves III-VI. It is rare for other cranial nerves to be involved, although this has previously been reported. We report a 19-year-old woman presenting with typical features of Tolosa-Hunt syndrome but ultimately developing bilateral facial nerve palsies and enhancement of both facial nerves on magnetic resonance imaging. The patient presented with unilateral retro-orbital headaches and palsies of cranial nerves III-VI. She was diagnosed with Tolosa-Hunt syndrome but was non-compliant with her corticosteroid treatment due to side effects. She returned with progressive left followed by right facial nerve palsy. Her corresponding follow-up magnetic resonance imaging scans showed sequential enhancement of the left and right facial nerves. She ultimately had clinical improvement with IV methylprednisolone. To our knowledge, Tolosa-Hunt syndrome associated with bilateral facial nerve palsy and corroborative facial nerve enhancement on magnetic resonance imaging has not previously been described. Moreover, our patient's clinical course is instructive, as it demonstrates that this atypical presentation of Tolosa-Hunt syndrome can indeed respond to corticosteroid treatment and should not be mistaken for other entities such as Bell's palsy.

Contralateral Depressor Labii Inferioris Chemodenervation for Congenital Unilateral Lower Lip Palsy.

INTRODUCTION: Congenital unilateral lower lip palsy - also known as asymmetric crying facies - is isolated asymmetry of the lower lip unilaterally. It is characterized by isolated lower lip asymmetry during smiling and speech. Although etiology is unknown, depressor labii inferioris (DLI) weakness is hold responsible. AIM: Purpose of this study was to evaluate the effectiveness of contralateral depressor labii inferioris botulinum toxin injection on patients' concern levels and patient satisfaction. Ten units of botulinum toxin A injection was carried out to the healthy contralateral side. METHODOLOGY: Eleven patients were treated. Patients' pretreatment and posttreatment concern regarding asymmetry during speech and smiling was evaluated with a questionnaire. Patients' perception of treatment satisfaction was also evaluated with a questionnaire. RESULTS: Mean score related to concern about asymmetric appearance during smiling decreased from 1.6 ±â€Š0.8 to 0.5 ±â€Š0.5. Mean score related to concern about asymmetric appearance during speech decreased from 1.6 ±â€Š0.5 to 0.4 ±â€Š0.5. Eleven out of 11 patients reported improvement with speech whereas 10 out of 11 patients reported improvement with smiling. No weakness about oral competence was reported. CONCLUSION: Most congenital unilateral lower lip palsy patients are concerned regarding their asymmetric appearance while smiling or speaking. Chemodenervation of the contralateral DLI muscle reduces concern levels and has high patient satisfaction. Chemodenervation of the contralateral healthy DLI muscle is a valid, practical treatment option.